title: Identification and characterization of the cuevaene A biosynthetic gene cluster in streptomyces sp. LZ35.
abstract: Genome sequence analysis of Streptomyces sp. LZ35 has revealed a large number of secondary metabolite pathways, including one encoded in an orphan type I polyketide synthase gene cluster that contains a putative chorismatase/3-hydroxybenzoate synthase gene. Mutagenesis and comparative metabolic profiling led to the identification of cuevaene A as the metabolic product of the gene cluster, thus making it the first 3-HBA containing polyketide biosynthetic gene cluster described to date. Cuv10 was proven to be responsible for the conversion of chorismate into 3-HBA; Cuv18 is speculated to be responsible for the 6-hydroxylation of 3-HBA during polyketide chain elongation. Additionally, several pathway-specific regulatory factors that affect the production of cuevaene A were identified. Our results indicate that targeted inactivation of a gene followed by comparative metabolic profiling is a useful approach to identify and characterize cryptic biosynthetic gene clusters.
authors.affiliation: State Key Laboratory of Microbial Technology, School of Life Science, Shandong University, No. 27 Shanda South Road, Jinan 250100, P. R. China.
authors.forename: Yuhai
authors.initials: Y
authors.lastname: Jiang
authors.forename: Haoxin
authors.initials: H
authors.lastname: Wang
authors.forename: Chunhua
authors.initials: C
authors.lastname: Lu
authors.forename: Yanjiao
authors.initials: Y
authors.lastname: Ding
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Li
authors.forename: Yuemao
authors.initials: Y
authors.lastname: Shen
mesh_terms: D001572:Benzofurans / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000235:genetics; D015394:Molecular Structure; D005810:Multigene Family; D013302:Streptomyces / Q000145:classification / Q000235:genetics*
chemical_list: D001572:Benzofurans; D005231:Fatty Acids, Unsaturated; C410789:cuevaene A
keywords: 3-hydroxybenzoate synthase; antibiotics; biosynthesis; cuevaene A; orphan gene cluster